Prepared By: Vijay Kumar

Affects > 780,000 persons per year3rd major cause of death & long-term disabilityEstimated U.S. cost for 2008 = $65.5 billion

In Trivandrum, annual incidence rates was 135/100 000

Stroke. 2009;40:1212-1218

Pre-hospital managementInitial assessment and emergency managementThrombolysisAcute stroke interventionMedical supportAntiplatelet agentsAnticoagulationSurgery

0102030405060708090minutes

Time is Brain

Diminishing Returns over TimeFavorable Outcome (mRS 0-1, BI 95-100, NIHH 0-1) at Day 90 Adjusted odds ratio with 95% confidence interval by stroke onset to treatment time (OTT) ITT population (N=2776)Pooled Analysis NINDS tPA, ATLANTIS, ECASS-I, ECASS-II~4h 40minCourtesy Brott T et alNNT 5

NNT 20

Penumbra damaged by: HypoperfusionHypoxiaAcidosis Hyperglycemia Fever Seizure

Guidelines Ischaemic Stroke 2008Emergency care in acute stroke depends on a four-step chain: Rapid recognition of, and reaction to, stroke signs and symptoms

Immediate EMS contact and priority EMS dispatch

Priority transport with notification of the receiving hospital

Guidelines Ischaemic Stroke 2008

Stroke vs Stroke mimikers

Time of onset of the stroke

Brief clinical evaluation, NIHSS score

Vitals, Blood sugar by glucometer

Check list for thrombolysis

Imaging

Is it stroke?Type of stroke

Cranial Computed Tomography (CT)Immediate plain CT scanning distinguishes reliably between haemorrhagic and ischaemic strokeDetects signs of ischaemia as early as 2 h after stroke onset

Helps to identify other neurological diseases (e.g. neoplasms)Most cost-effective strategy for imaging acute stroke patients

Wardlaw J et al. Stroke (2004) 35:2477-2483von Kummer R et al. Radiology (2001) 219:95-100

HYPERACUTE STROKE ON CTEARLY ISCHEMIC CHANGES (EIC)HYPERDENSE MIDDLE CEREBRAL ARTERY (HDMCA)ATTENUATION OF LENTIFORM NUCLEUS (ALN)LOSS OF INSULAR RIBBON (LIR)EFFACEMENT OF SULCILOSS OF CM DIFFERENTIATIONWINDOW PERIOD UPTO 6 HOURS

INSULAR RIBBON?

Hyperdense MCA sign (HMCAS)NCCTCTA

MCA dot signNCCTCTASpecificty-100% : Sensitivity -38%Leary MC Stroke 2003;34:2636-40

86 year old with acute onset of rt side weakness,leg more weak than arm and difficulty in speech ,came in 1.5 hrs of onset. CT scan shows hyperdense left ACA. CTA shows clot in left ACAHyperdense ACA

Hyderdense ICA (HICAS)Specificity 100%Ozdemir O et al.Stroke 2008;39:2011-16.

52 yr old with acute diplopia and ataxia and left INO .CTA shows thrombus in the top of basilar and left P1 occluded. Basilar artery thrombus

M1

8-10 8-10 8-10 3-7 4-7 4-7 0-2 0-3 0-3 NINDS ATLANTIS ECASS-2 NINDS ATLANTIS ECASS-2 NINDS ATLANTIS ECASS-2

ASPECTSn 201 424 280 89 104 119 10 21 5

DISADVANTAGE OF CTLess sensitive than MRI

Posterior fossa stroke

Stroke mimics diagnosis is inferior to MRI

Window period 3 to 6 hours- identification of penumbra not possible

Diffusion-weighted MRI (DWI) is more sensitive for detection of early ischaemic changes than CTPosterior circulation strokeDetects even small intracerebral haemorrhages reliably on T2* sequencesMRI is particularly important in acute stroke patients with unusual presentations

In most instances, CT will provide the information to makedecisionsabout emergency management (Class I, Level of EvidenceA). The brain imaging study should be interpreted by a physicianwith expertise in reading CT or MRI studies of the brain (ClassI, Level of Evidence C).

Multimodal CTand MRI may provide additional information thatwill improvediagnosis of ischemic stroke (Class I, Level ofEvidence A).

Class II RecommendationsVascular imagingis necessary as a preliminary step for intra-arterialadministrationof pharmacological agents, surgical procedures,or endovascularinterventions (Class IIa, Level of EvidenceB).

Class III Recommendations Emergency treatment of stroke should not be delayed in orderto obtain multimodal imaging studies (Class III, Level of EvidenceC).

Vascular imaging should not delay treatment of patients whosesymptoms started

I. Triage10 minReview t-PA criteriaPage acute stroke teamDraw pre t-PA labsII. Medical Care25 minPlace O2 , 2 NS IVsObtain BP, weight, NIHSSObtain 12-lead ECGSend patient to CT

III. CT & Labs45 minObtain lab resultsRead CTReturn pt to EDIV. Treatment60 minStart IV t-PAMonitor for ICH sxsHTN, headache neuro status

IV thrombolysisNINDS, ECASS I + II, ATLANTISThe ATLANTIS, ECASS and NINDS rt-PA Study Group Investigators, Lancet 2004

OTTOdds Ratio for normal at 3 mo. Hemorrhage0-1.5 h2.813.1%1.5-3 h1.555.6%3-4.5 h1.405.9%4.5-6 h1.156.9%

Infuse 0.9 mg/kg (maximum dose 90 mg) over 60 minutes 10% of the dose given as a bolusNeurological assessments every 15 minutes during the infusion every 30 minutes thereafter for the next 6 hourshourly until 24 hours after treatment

Discontinue the infusion if worsening, raised ICP features Obtain emergency CT scan.

Measure blood pressure every 15 minutes for the first 2 hours every 30 minutes for the next 6 hourshourly until 24 hours after treatment.Delay placement of nasogastric tubes, indwelling bladder catheters, or intra-arterial pressure catheters.Follow-up CT scan at 24 h before starting anticoagulants or antiplatelet agents.

ECASS III

Hacke, N Engl J Med 2008*OR 1.34 (1.02-1.74) P = 0.04**p = 0.006

% Normal at 3 mo.*Symptomatic ICH**tPA52%2.4%Placebo**45%0.2%

< 3.0 HoursNo upper age limitNo limit on stroke sizeCan give if taking warfarin & INR < 1.73.0-4.5 HoursDo NOT give if:Pt > 80 yrNIHSS > 25DM / previous strokeTaking warfarin at all

Mismatch Concept

Treatment need to be individualised

Heterogeneous Disease: Infarction at different rates 1 Hr 3 Hr6 Hraverageslowfast

CT perfusionMuir KW et al. Lancet Neurology 2006; 5:755-768

ParametersDefinition of PenumbraAdvantagesLimitationsCT PerfusionCBF, CBV, MTT, TTPMTT threshold at 145% Combined with plain CTAvailableFastLimited brain coveragePoorly sensitive to posterior circulationIodonated contrastDWI-PWI MRICBF, CBV, MTT, TTP, ADCRelative TTP (or MTT) delay >45s and normal DWISensitiveNo radiationLimited availabilityPatient cooperation requiredFrequent contraindications

Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE)

Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET)Lancet Neurol2008;7:299309. Lancet Neurol2008;7:299309.

Ann Neurol. 2006 Nov;60(5):508-17

N = 101

RCT Placebo controlled non-significantly lower rates of infarct growth were seen in PWI/DWI mismatch patients who received rt-PA

Contraindication for IV thrombolysisStroke onset ; anterior circulation ; 6-8 hrsPosterior circulation stroke (12-24 hrs)Concomitant vascular stenosis or dissection/Large vessel occlusionPoor NIHSS score > 20 Large salvageable territory (>20% on perfusion imaging)Hyperdense MCA signSuspected hard embolus (calcified debris)

Intra-arterial thrombolysis

Bridging therapy(0.6 mg/kg IV) + (10-22 mg IA);

Mechanical thrombolysis

EKOS - MicroLys infusion catheter (EKOS) Neurosurg Clin N Am.2009 Oct;20(4):419-29

FDA-approved for recanalizing acutely occluded cerebral arteries. Multi-MERCI study - Patients who did not improve immediately after IV rt-PA underwent mechanical embolectomy within 8 hours of symptom onset. Partial or complete recanalization occurred in 74% of patients, Symptomatic intracerebral hemorrhage (sICH) rate of 6.7%.

Baseline angiogram demonstrates complete occlusion of the right ICA terminus (black arrow).

Post treatment angiogram demonstrates complete reperfusion of the right ICA territory after 1 pass of the Merci L6 device.

Available in 3 different sizes aimed to treat different vessel diameters.Thromboaspiration is achieved by connecting the microcatheter (black arrows) to an aspiration pump. The separator (white arrows) is then advanced in and out of the microcatheter tounclog any obstructive thrombus.

Autoregulation is impaired/abolished in stroke.CBF follows perfusion pressure

Blood pressure>220 systolic or > 120 dystolic BP only needs emergency treatment if no end organ damage

Hypertensive encephalopathySymptomatic ischemic heart diseaseCongestive cardiac failureRapidly progressive renal dysfunctionBefore and after thrombolytic therapyDeterioration of patient due to hmgic conversion of infarct.Aortic dissection

Guidelines for the Early Management of Adults With Ischemic Stroke, AHA/ASA Guideline, Stroke. 2007

Ideal Drug Short acting easily titrated predictable responseDrug used Labetolol Nicardipine infusionsodium nitroprusside (if refractory)Avoid Drugs that dilate intracranial vessels and increase ICT .e.g. -nitroglycerineUse of nifidepine strongly discouraged

HypoglycemiaMimickerCan compromise penumbra

HyperglycemiaRelated to poor outcome in both thrombolysis and non-thrombolysis patients

Majority of trials addresses secondary prevention2 major trials (International Stroke Trial (IST) and Chinese Acute Stroke Trial (CAST)] evaluated the benefit of aspirin in AISassociated with a significant reduction in death or dependence (OR 0.95, 95% CI 0.91 to 0.99; p=0.008) and recurrent ischemic strokes (OR 0.77, 95% CI 0.68 to 0.86; p

Asprin 150-325 mg to be given within 24-48 hrs (Class I, Level of Evidence A)

Fast Assessment of Stroke and Transient Ischemic Attack to Prevent Early Recurrence (FASTER) pilot trial Trend towards better benefit with clopidogrel + Asprin but no statastical significance

Stroke. 2007;38:1655-1711

HeparinControversialMeta-analysis of 24 trials involving 23748 participants showed no benefit with regards to death and dependency or death alone in patients with AISCochrane Database Syst Rev2008Not recommended in acute ischemic stroke

Cochrane Database Syst Rev2008 Cochrane Database Syst Rev2008 Cochrane Database Syst Rev2008

Low molecular weight heparinNo benefit on stroke outcome for low molecular heparin (nadroparin, certoparin, tinzaparin, dalteparin) Heparinoid (orgaran)TOAST trial neutralTOAST Investigators: JAMA (1998) 279:1265-72.

High dose statinsSPARCL studyrecent stroke or TIA without known coronary heart disease, 80 mg of atorvastatin per day reduced the overall incidence of strokes and of cardiovascular events, despite a small increase in the incidence of hemorrhagic stroke.

Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. N Engl J Med 2006

Admission shortly after ictusElevated systolic BP of >160mm Hg (Broderick J, Stroke 2007)Irregular shape of clotLiver dysfunctionCoagulation abnormalitiesMarkers of vascular injury & inflammation (high TLC, fibrinogen levels, low platelet count, high levels of IL-6, TNF-, MMP-9, c-Fn)

ICH on Heparin Protamine sulphate 1 mg/100 units of heparinICH - on Warfarin 5-25 mg Vitamin K1FFP (10-20 ml/ kg)Recombinant factor VIIaICH on Thrombolytic therapy 4 -6 units of cryoprecipitate or FFP

The INTERACT study, 2008: showed a trend toward lower relative and absolute growth in hematoma volumes from baseline to 24 hours in the intensive treatment group compared with the control group.

In addition, there was no excess of neurological deterioration or other adverse events related to intensive BP lowering.

The study provides an important proof of concept for early BP lowering in patients with ICH, but the data are insufficient to recommend a definitive policy.

Another study, the Antihypertensive Treatment in Acute Cerebral Hemorrhage (ATACH) trial,also confirms the feasibility and safety of early rapid BP lowering in ICH. Ref: Anderson CS, Huang Y, Wang JG et al. INTERACT Investigators. Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial. Lancet Neurol. 2008

Class II b , Level of evidence C

Management of raised ICP

Cerebellar hematoma > 3 cms or > 40 mlVermian hematomalobar clots >30 mL and within1 cm of the surface

For rest of the ICH, surgery is uncertain

SIHCPARCT -200371 pts, 36 randomised to surgeryStatistically significant reduction in the volume of clotNo reduction in mortality at 6 monthsHigh risk of rebleeding 22%MISTIERCT , 2007 ongoingClot reduction in 46% in surgery arm vs 4% in control armAdverse events within safety limits

rtPA, urokinase

May improve survival significantly(Cochrane Database Syst Rev 2002;(3))

Clear IVH trial (Clot Lysis Evaluating Accelerated Resolution of IVH)

Appears to have a fairly low complication rate, efficacy and safety of this treatment is uncertain and is considered investigational (Class IIb; Level of Evidence: B)

Acute stroke treatment should be initiated as early as possible

IV thrombolysis to be administered at the earliest in eligible candidates Medical management to be optimized to ensure adequate perfusion of penumbra

Adams HP et. al., Guidelines for the Early Management of Adults With Ischemic Stroke. AHA/ASA Guideline. Stroke.2007;38:1655

Novakovic R et. al. Review of current and emerging therapies in acute ischemic stroke. J NeuroIntervent Surg2009

Guidelines for Management of Ischaemic Stroke and Transient Ischaemic Attack 2008. Available at http://www.esostroke.org

Indications for the Performance of Intracranial Endovascular Neurointerventional Procedures. AHA scientific statement. Circulation. 2009;119:2235-2249

Morgenstern LB et. al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage. AHA/ASA guideline. Stroke.2010;41:2108

ASPECTS 25Age > 65Coronary A. Disease

Hypertension should not be aggressively treated unless SBP > 220Short acting antihypertensive to be usedNitroglycerine infusion is recommended for BP control during IV thrombolysisAggressive reduction in BP associated with poor outcome

Thalamic bleedIntraventricular bleedLobar ICH Brainstem bleed

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